Implantable valve device

ABSTRACT

Valve devices, methods of making valve devices, and methods of treating various venous-related conditions, disorders and/or diseases are described. In one embodiment, a valve device includes an expandable support frame and a bioprosthetic valve attached to the support frame. The bioprosthetic valve comprises a leaflet and a contiguous wall portion harvested from a multi-leaflet xenogeneic valve. The contiguous wall portion includes the attachment region where the leaflets attaches to the vessel wall and, in some embodiments, includes the natural margins of attachment between the leaflet and vessel wall.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/414,794, which was filed on Jan. 25, 2017, which is a continuation ofU.S. patent application Ser. No. 12/252,918, which was filed on Oct. 16,2008, which claims priority to U.S. Provisional Application No.60/980,770, filed on Oct. 17, 2007. The entire contents of each of theserelated applications are hereby incorporated by reference into thisdisclosure.

FIELD

The disclosure relates generally to the field of implantable medicaldevices useful in the regulation of fluid flow through a body vessel.Particular embodiments relating to venous valve devices, the methods ofmaking such devices, and methods of treating various venous-relatedconditions, disorders and/or diseases, including venous insufficiencyare described in detail.

BACKGROUND

Many vessels in animal bodies transport fluids from one bodily locationto another. Typically, fluid flows in a unidirectional manner along thelength of the vessel. Varying fluid pressures over time, however, canintroduce a reverse flow direction in the vessel. In some vessels, suchas mammalian veins, natural valves are positioned along the length ofthe vessel and act as one-way check valves that open to permit the flowof fluid in the desired direction and close to prevent fluid flow in areverse direction, i.e., retrograde flow. The valves can change from anopen position in response to a variety of circumstances, includingchanges in the cross-sectional shape of the vessel and the fluidpressure within the vessel.

While natural valves may function for an extended time, some may loseeffectiveness, which can lead to physical manifestations and pathology.For example, venous valves are susceptible to becoming insufficient dueto one or more of a variety of factors. Over time, the vessel wall maystretch, affecting the ability of the valve leaflets to close.Furthermore, the leaflets may become damaged, such as by formation ofthrombus and scar tissue, which may also affect the ability of the valveleaflets to close. Once valves are damaged, venous valve insufficiencymay be present, and can lead to discomfort and possibly ulcers in thelegs and ankles.

Current treatments for venous valve insufficiency include the use ofcompression stockings that are placed around the leg of a patient in aneffort to force the vessel walls radially inward to restore valvefunction and various surgical techniques in which valves are bypassed,eliminated, or replaced with autologous sections of veins havingcompetent valves. Drastic ablation procedures, including laser ablation,vein ligation and stripping, are also frequently employed.

Other areas of medicine have benefitted greatly over recent years fromthe development of minimally invasive techniques and instruments forplacement of intraluminal medical devices. A wide variety of treatmentdevices that utilize minimally invasive technology has been developedand includes stents, stent grafts, occlusion devices, infusion cathetersand the like. Minimally invasive intravascular devices have especiallybecome popular with the introduction of coronary stents to the U.S.market in the early 1990s. Coronary and peripheral stents have beenproven to provide a superior means of maintaining vessel patency, andhave become widely accepted in the medical community. Furthermore,stents have been adapted for use in a variety of other treatments andmedical devices.

Several researchers have pursued the development of prosthetic valvesthat are implantable by minimally invasive techniques over recent years.Indeed, the art now contains several examples of implantable cardiac andvenous valve devices. Many of these prior art devices include anexpandable support frame and an attached graft member that is fashionedinto a valve that regulates fluid flow through the device and,ultimately, a body vessel. For example, a graft member can be in theform of a leaflet that is attached to a support frame and movablebetween first and second positions. In a first position, the valve isopen and allows fluid flow to proceed through a vessel in a firstdirection, and in a second position the valve is closed to prevent fluidflow in a second, opposite direction. Examples of this type ofprosthetic valve are described in commonly owned U.S. Pat. No. 6,508,833to Pavcnik for a MULTIPLE-SIDED INTRALUMINAL MEDICAL DEVICE, UnitedStates Patent Application Publication No. 2001/0039450 to Pavcnik for anIMPLANTABLE VASCULAR DEVICE, and U.S. patent application Ser. No.10/642,372, filed on Aug. 15, 2003, each of which is hereby incorporatedby reference in its entirety. In other examples, a tube-like graftmember that terminates in leaflets is used. The graft member is attachedto one or more support frames to form a valve. The leaflets open topermit fluid flow in a first direction in response to fluid pressure onone side of the leaflets and close to prevent fluid flow in a second,opposite direction in response to fluid pressure on opposite sides ofthe leaflets. An example of this configuration is provided in U.S. Pat.No. 6,494,909 to Greenhalgh for AN ENDOVASCULAR VALVE, which is herebyincorporated by reference in its entirety.

Despite these and other examples, a need remains for improvedimplantable valve devices, methods of making such devices, and methodsof treating various venous-related conditions, disorders and/ordiseases.

SUMMARY OF EXEMPLARY EMBODIMENTS

Valve devices, methods of making valve devices, and methods of treatingvarious venous-related conditions, disorders and/or diseases aredescribed.

A valve device according to an exemplary embodiment of the inventioncomprises an expandable support frame and a bioprosthetic valve attachedto the support frame. The bioprosthetic valve comprises a single leafletharvested from a natural valve and a contiguous wall portion attached tothe leaflet. In exemplary embodiments, the contiguous wall portionincludes the portion of the vessel wall that defines the natural sinusfor the leaflet. While the bioprosthetic valve can be harvested from anysuitable source, the use of porcine valves, such as an aortic porcinevalve, is considered advantageous.

The support frame is an expandable support frame that includes one ormore struts. In exemplary embodiments, the support frame defines awindow portion substantially free of the struts. The window portion ispositioned such that the leaflet of the attached bioprosthetic valve isable to close against a portion of an inner wall of said recipientvessel.

In exemplary embodiments, the support frame defines an outwardlyprojecting portion configured to create a sinus region in the recipientvessel upon implantation therein.

A valve device according to one exemplary embodiment comprises abioprosthetic valve comprising a single leaflet harvested from a donorvalve and a contiguous wall portion, and an expandable support framecomprising one or more struts and defining an outwardly projectingportion configured to outwardly deflect a portion of the inner wall ofthe recipient vessel upon implantation therein. The bioprosthetic valveis attached to the support frame and, in this embodiment, the baseportion of the leaflet is positioned substantially adjacent theoutwardly projecting portion such that a valve sinus region is formedbetween the outwardly deflected portion of the inner wall of therecipient vessel and the leaflet.

A valve device according to another embodiment comprises an expandablesupport frame comprising one or more struts, the support frame definingan outwardly projecting portion configured to create a sinus region insaid recipient vessel upon implantation therein and a window portionsubstantially free of the one or more struts; and a bioprosthetic valvecomprising a natural valve leaflet harvested from a donor valve and acontiguous wall portion. In this embodiment, the bioprosthetic valve isattached to the support frame such that the leaflet is positionedsubstantially opposite the window portion when the valve is in an openposition. Advantageously, this structure allows the leaflet tosubstantially close against a portion of an inner wall of the recipientvessel.

A valve device according to another embodiment comprises an expandablesupport frame defining an outwardly projecting portion configured tocreate a sinus region in a recipient vessel upon implantation thereinand a window portion substantially free of the one or more struts; and abioprosthetic valve attached to the support frame. The bioprostheticvalve comprises a noncoronary leaflet and a contiguous wall portionharvested from a xenogeneic aortic valve. The device also includes atleast one suture attaching the contiguous wall portion to the supportframe along an attachment pathway and passing through only a partialthickness of the contiguous wall portion at at least one point on theattachment pathway. The bioprosthetic valve is attached to the supportframe such that the leaflet is positioned substantially opposite thewindow portion when the valve is in an open position.

Methods of making valve devices are also described. A method accordingto an exemplary embodiment comprises the steps of fabricating abioprosthetic valve and attaching the bioprosthetic valve to a supportframe. In one exemplary method, the step of fabricating a bioprostheticvalve includes the steps of providing a suitable xenogeneic valve,selecting a suitable leaflet, and excising tissue from the valve toleave a contiguous wall portion attached to the selected leaflet thatincludes the natural margins of attachment where the leaflet attaches tothe vessel wall. The method can also include a step of reducing thethickness of the contiguous wall portion, such as by shaving or byanother suitable technique.

In an exemplary method of making a valve device, a leaflet associatedwith the noncoronary sinus, also known as the posterior aortic sinus, ofa xenogeneic aortic valve is selected.

Delivery systems for percutaneously delivering a valve device to adesired point of treatment in a recipient vessel are also provided. Anexemplary delivery system comprises an elongate member having a proximalend, a distal tip adapted for insertion into and navigation through arecipient vessel, and a length from the proximal end to the distal tip.The elongate member includes a device chamber into which an expandablemedical device can be disposed. A sheath is disposed about the elongatemember and over the device chamber, and is adapted to slidably movealong the length of the elongate member. A valve devices according to anembodiment of the invention, such as the exemplary embodiment describedabove, is disposed within the device chamber.

Additional understanding can be obtained with review of the detaileddescription of exemplary embodiments, appearing below, and the appendeddrawings illustrating exemplary embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a front perspective view of a bioprosthetic valve suitablefor use in valve devices according to the invention.

FIG. 1B is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 1C is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 2A is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 2B is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 2C is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 2D is a front perspective view of an alternate bioprosthetic valvesuitable for use in valve devices according to the invention.

FIG. 3 is a perspective view of a valve device according to a firstexemplary embodiment.

FIG. 4 is an end view of the valve device illustrated in FIG. 3 . Thebioprosthetic valve of the device is shown in an open configuration.

FIG. 5 is an end view of the valve device illustrated in FIG. 3 . Thebioprosthetic valve of the device is shown in a closed configuration.

FIG. 6 is a side view of a valve device according to a second exemplaryembodiment.

FIG. 7 is a top view of the valve device illustrated in FIG. 6 .

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The following detailed description and the appended drawings describeand illustrate various exemplary embodiments of the invention. Thedescription and drawings are exemplary in nature and are provided toenable one skilled in the art to make and use one or more embodiments ofthe invention. They are not intended to limit the scope of theinvention, or its protection, in any manner.

The invention provides implantable valve devices useful in regulatingfluid flow through a body vessel of a patient, such as a human or otheranimal. Valve devices according to the invention include a bioprostheticvalve attached to a support frame.

As used herein, the term ‘valve device’ refers to an implantable medicaldevice that includes a bioprosthetic valve attached to a support frame.

As used herein, the term ‘bioprosthetic valve’ refers to a valvecomprising at least one leaflet and a contiguous wall portion harvestedfrom a natural valve, such as a multi-leaflet vascular valve harvestedfrom a xenogeneic source. The contiguous wall portion includes tissuetaken from the natural valve at a natural attachment margin where theleaflet attaches to a vessel wall. The size and configuration of thecontiguous wall portion varies between valve devices according toembodiments of the invention, as described below.

U.S. Non-provisional patent application Ser. No. 12/252,253, filed byDr. Norman Jaffe of Dana Point, Calif. on Oct. 15, 2008, and entitled“BIOLOGICAL VALVE FOR VENOUS VALVE INSUFFICIENCY,” describes variousbioprosthetic valves suitable for use in valve devices according to theinvention. The entire contents of this application are herebyincorporated into this disclosure for the purpose of describing suitablebioprosthetic valves, and their preparation, for inclusion in valvedevices according to embodiments of the invention.

FIGS. 1A, 1B, and 1C illustrate three different bioprosthetic valvessuitable for use in valve devices according to embodiments of theinvention. The illustrated bioprosthetic valves are described fully inthe incorporated 60/980,708 application and will only be describedbriefly herein. In each bioprosthetic valve illustrated in theseFigures, the contiguous wall portion comprises a patch of tissue thatextends axially, with respect to the source vessel and host vessel,above and below the leaflet and laterally on both sides of the leaflet.Use of this type of bioprosthetic valve might be advantageous in valvedevices according to particular embodiments of the invention.

The bioprosthetic valve 100 illustrated in FIG. 1A includes a singleleaflet 102 attached to a patch 104 of tissue at attachment region 106.The leaflet 102 has a free edge 103 which moves in response to differingpressures in the body vessel in which the bioprosthetic valve 100 isdisposed to open and close the valve 100.

The patch 104 extends axially (with respect to the source vessel andhost vessel) above and below the leaflet 102 to provide upper and lowerregions 108(a), 108(b) for attaching the bioprosthetic valve 100 to asupport frame in a valve device according to embodiments of theinvention, as described below. If the bioprosthetic valve is from anaortic valve source, the patch 104 may include a segment of the aorticannulus and/or a segment of the aortic wall.

The patch 104 also extends circumferentially on either side of theleaflet 102 to provide lateral regions 110(a), 110(b) for attaching thebioprosthetic valve 100 to a support frame in a valve device accordingto embodiments of the invention, as described below. The regions 110(a),110(b) may extend only minimally beyond the region of the leaflet 102,as shown in FIG. 1 , or may extend further so as to partially orentirely encircle a circumferential support frame to which thebioprosthetic valve 100 is attached and a body vessel into which thebioprosthetic valve 100 is disposed. It is noted that, while thecontiguous wall portion 104 extends in circumferential directions oneither side of the leaflet 102, it advantageously does not extend toinclude a complete circumferential path on the circumference of thesource vessel. Indeed, a contiguous wall portion comprising anon-circumferential portion of the source vessel wall is consideredadvantageous at least because it reduces the bulk of the resulting valvedevice, as described more fully below.

The patch 104 may be generally rectangular, as shown in FIG. 1 , or mayhave any other suitable shape (such as circular, oval, or oblong). Thespecific shape chosen for the patch portion of the bioprosthetic valvein a valve device according to a particular embodiment of the inventionwill depend on various considerations, including the shape and/orconfiguration of the support frame included in the valve device. Askilled artisan will be able to select an appropriate shape for thepatch based on these and/or other considerations.

It is noted that, while illustrated with the regions 108(a), 108(b) and110(a), 110(b) extending substantially symmetrically above and below andon either side of the leaflet 102, the patch 104 can of course extendabout the leaflet 102 by different lengths in different directions.

The bioprosthetic valve 100 and its leaflet 102 may be selected andconfigured so that, with the valve 100 attached to a support frame in avalve device, as described below, and in a closed position, the leaflet102 provides adequate obstruction of the host body vessel at the pointat which the valve device is disposed. The leaflet 102 need not,however, be selected or configured to completely obstruct the host bodyvessel in the closed position, as some degree of retrograde flow may beacceptable and even desirable. Accordingly, with the bioprosthetic valve100 in a closed position, the free edge 103 of the leaflet 102 may (butneed not) contact an opposing portion of an attached support frameand/or an opposing wall of the host body vessel, either partially orcontinuously along the length of the free edge 103.

The bioprosthetic valve 100 according to the embodiment illustrated inFIG. 1 , and indeed all embodiments, may comprise tissue from anysuitable xenogeneic source, such as porcine, bovine, or equine tissue.Porcine, bovine, and equine heart tissue is considered to beadvantageous. Porcine heart tissue is considered particularlyadvantageous at least because of its ready availability and generalacceptance as a suitable source of xenogeneic tissue. Also, theinventors have determined that the leaflets of porcine heart valves havesizes and configurations that render them suitable for use as venousvalves in human patients.

FIG. 1B illustrates an alternative bioprosthetic valve 150 suitable foruse in valve devices according to embodiments of the invention. Thevalve 150 has a single leaflet 152 attached to a patch 154 at attachmentregion 156 and has a free edge 153 that moves in response to differingpressures in the host body vessel to open and close the valve 150.

The patch 154 has a generally ovoid shape which extends axially (withrespect to the source vessel and host vessel) above and below theleaflet 152 to provide upper and lower regions 158(a), 158(b) forattaching the bioprosthetic valve 150 to a support frame in a valvedevice according to embodiments of the invention, as described below.Similarly, the patch also extends circumferentially on either side ofthe leaflet 152, to provide lateral regions 160(a), 160(b) for attachingthe bioprosthetic valve 150 to a support frame in a valve deviceaccording to embodiments of the invention, as described below.

FIG. 1C illustrates an alternative bioprosthetic valve 170 suitable foruse in valve devices according to embodiments of the invention. Thevalve 170 has a single leaflet 172 attached to a patch 174 at attachmentregion 176 and has a free edge 173 that moves in response to differingpressures in the host body vessel to open and close the valve 170.

The patch 174 has a generally lenticular shape which extends axially(with respect to the source vessel and host vessel) above and below theleaflet 172 to provide upper and lower regions 178(a), 178(b) forattaching the bioprosthetic valve 170 to a support frame in a valvedevice according to embodiments of the invention, as described below.Similarly, the patch also extends circumferentially on either side ofthe leaflet 172, to provide lateral regions 180(a), 180(b) for attachingthe bioprosthetic valve 170 to a support frame in a valve deviceaccording to embodiments of the invention, as described below. As shownin the Figure, the upper and lower regions 178(a), 178(b) may includepointed or angled sections to facilitate attachment of the bioprostheticvalve 170 to a support frame and/or a body vessel into which a valvedevice including the bioprosthetic valve is disposed.

FIGS. 2A, 2B, 2C, and 2D illustrate three alternate bioprosthetic valvessuitable for use in valve devices according to embodiments of theinvention. In each bioprosthetic valve illustrated in these Figures, thecontiguous wall portion comprises a section of tissue having a lateraledge that extends along a path similar to the contour of an interfacebetween the leaflet and contiguous wall portion. Also, the contiguouswall portion extends slightly beyond the interface to include thenatural margins of attachment between the leaflet and vessel wall.

The bioprosthetic valve 200 illustrated in FIG. 2A includes a singleleaflet 202 attached to a contiguous wall portion 204 having an outeredge 205 that extends along a path similar to the contour of theinterface 207 between the leaflet 202 and contiguous wall portion 204.The leaflet 202 has a free edge 203 that moves in response to differingpressure in the body vessel in which the bioprosthetic valve 200 isdisposed. This movement of the free edge 203 of the leaflet 202 effectsopening and closing of the valve 200. In this embodiment, an innersurface 215 of the leaflet 202 and an inner surface 217 of thecontiguous wall portion 204 define a valve pocket 220 that opens andcloses as the free edge 203 moves.

In this embodiment, the contiguous wall portion 204 extends tosubstantially the same axial height, with respect to the source and hostvessels, as the free edge 203 of the leaflet 202. This configuration ofthe contiguous wall portion 204 is considered advantageous at leastbecause it provides a fixed tissue surface for the leaflet 203 tointeract with as it moves and avoids interaction with the natural wallof the host vessel, which may be diseased and/or weakened.

The bioprosthetic valve 250 illustrated in FIG. 2B is similar to thevalve 200 illustrated in FIG. 2A, except as described below. Thus, thevalve 250 has a single leaflet 252 attached to a contiguous wall portion254 having an outer edge 255 that extends along a path similar to thecontour of the interface 257 between the leaflet 252 and contiguous wallportion 254. The leaflet 252 has a free edge 253 that moves in responseto differing pressure in the body vessel in which the bioprostheticvalve 250 is disposed. In this embodiment, an inner surface 265 of theleaflet 252 and an inner surface 267 of the contiguous wall portion 254define a valve pocket 269 that opens and closes as the free edge 253moves.

In this embodiment, the contiguous wall portion 254 extends beyond theaxial height of the free edge 253 of the leaflet 252. This configurationis considered advantageous at least because it provides the fixed tissuesurface for the leaflet to interact with, as in the embodimentillustrated in FIG. 2A, but also provides an additional fixed tissueportion above the free edge 253 which may help to avoid fluid flow thatpasses behind the wall portion 254 when the leaflet 252 closes.Furthermore, the contiguous wall portion 254 in this embodiment includessubstantially all of the tissue that defines the natural sinus for theleaflet 252. This is considered advantageous at least because theinclusion of the natural sinus facilitates flushing of the valve pocket269 formed in the valve device 200, which is expected to enhance overallperformance of the device 200.

The bioprosthetic valve 270 illustrated in FIG. 2C is similar to thevalve illustrated in FIG. 2A, except as described below. Thus, the valve270 has a single leaflet 272 attached to a contiguous wall portion 274having an outer edge 275 that extends along a path similar to thecontour 277 of the interface between the leaflet 272 and contiguous wallportion 274. The leaflet 272 has a free edge 273 that moves in responseto differing pressure in the body vessel in which the bioprostheticvalve 270 is disposed. In this embodiment, an inner surface 285 of theleaflet 272 cooperatively defines a valve pocket 289 with an innersurface of the host vessel wall. The pocket 289 opens and closes as thefree edge 273 moves.

In this embodiment, the contiguous wall portion 274 comprises asubstantially U-shaped section of tissue that includes the naturalmargins of attachment between the leaflet 272 and wall portion 274 andextends only slightly beyond the interface between the leaflet 272 andwall portion 274. This configuration is considered advantageous at leastbecause it retains the natural attachment margins between the leaflet272 and the vessel wall, which has advantages, as described below, whileminimizing the overall amount of tissue included in the valve 270. Thismay minimize the bulk associated with a valve device that includes thebioprosthetic valve 270.

The bioprosthetic valve 290 illustrated in FIG. 2D is similar to thevalve illustrated in FIG. 2A, except as described below. Thus, the valve290 has a single leaflet 292 attached to a contiguous wall portion 294having an outer edge 295 that extends along a path similar to thecontour 297 of the interface between the leaflet 292 and contiguous wallportion 294. The leaflet 292 has a free edge 293 that moves in responseto differing pressure in the body vessel in which the bioprostheticvalve 290 is disposed. In this embodiment, an inner surface 298 of theleaflet 292 cooperatively defines a valve pocket 299 with an innersurface of the host vessel wall. The pocket 299 opens and closes as thefree edge 293 moves.

In this embodiment, the contiguous wall portion 294 comprises asubstantially U-shaped section of tissue that extends into the valvepocket 299 but that does not extend beyond the contour 297 of theinterface between the leaflet 292 and contiguous wall portion 294. Whilethis configuration may not include the complete margins of attachmentbetween the leaflet 292 and the contiguous wall portion 294, it providesa bioprosthetic valve 290 having less bulk than the other embodiments,which may be desirable in situations in which the overall circumferenceof a valve device is a point of concern, such as valve devices intendedfor delivery through and/or implantation in body vessels having smallinner diameters as compared to other body vessels.

In all embodiments, the inclusion of a contiguous wall portion thatincludes tissue taken from the donor vessel wall at an attachment regionwhere the leaflet attaches to the vessel wall is considered advantageousat least because the attachment region includes a unique microstructurethat is believed to enhance the ruggedness of the bioprosthetic valve inan implantable valve device. Retaining the natural margins of attachmentbetween the leaflet and vessel wall in the contiguous wall portion isconsidered particularly advantageous. For example, in an aortic valve,the margins of attachment, i.e., the leaflet anchorages, are composednearly exclusively of a dense collagenous tissue that provides a durableattachment between the leaflet and wall, which is expected to have abeneficial advantage on the longevity of a valve device that includes abioprosthetic valve that includes the margins of attachment.

Valve devices according to embodiments of the invention also include asupport frame. A wide variety of support frames are known in the medicaltechnology arts, and any suitable support frame can be utilized in avalve device according to an embodiment of the invention. The supportframe need only provide a surface to which the bioprosthetic valve canbe attached in a manner that allows the valve to function as describedherein. It is understood that the support frame need not have anyparticular structure and/or configuration and, indeed, can compriseminimal structure or distinct and independent structures attached to thebioprosthetic valve. For example, a support structure comprising one ormore barbs or microbarbs, known to those skilled in the art ofintraluminal medical devices, can be attached to the bioprosthetic valveand function as a support frame as contemplated herein.

As described below, the support frame advantageously comprises anexpandable support frame having radially compressed and radiallyexpanded configurations. Such a support frame can be implanted at apoint of treatment within a body vessel by minimally invasivetechniques, such as delivery and deployment with an intravascularcatheter. It is noted, though, that valve devices according toembodiments of the invention, regardless of the type and/or nature ofthe support frame, can be implanted by other techniques, includingsurgical techniques.

The support frame can optionally provide additional function to themedical device. For example, the support frame can provide a stentingfunction, i.e., exert a radially outward force on the interior wall of avessel in which the medical device is implanted. By including a supportframe that exerts such a force, a valve device according to theinvention can provide both a stenting and a valving function at a pointof treatment within a body vessel, which may be desirable in certainsituations, such as when a degree of vessel stenosis, occlusion, and/orweakening is present. A frame that provides an initial stenting functionthat decreases over time can also be used. Examples of such supportframes are described in United States Patent Application Publication No.20050228486 A1, entitled IMPLANTABLE FRAME WITH VARIABLE COMPLIANCE, theentire contents of which are hereby incorporated into this disclosurefor the purpose of describing suitable support frames for use in valvedevices according to the invention.

The stent art provides numerous support frames acceptable for use in thepresent invention, and any suitable stent can be used as the supportframe. The specific support frame chosen will depend on numerousfactors, including the body vessel in which the valve device is beingimplanted, the axial length of the treatment site within the vessel, theinner diameter of the vessel, the delivery method for placing themedical device, and other considerations. Those skilled in the art candetermine an appropriate support frame for use in a specific valvedevice according to a particular embodiment based on these and otherconsiderations as they exist in a particular body vessel and/or at aparticular point of treatment. For example, for a point of treatment atwhich primary venous insufficiency is determined, a valve device withminimal support frame structure and minimal outwardly-directed radialforce, such as the attached barbs and microbarbs described above, may bedesirable and/or suitable. Other points of treatment, such a those atwhich a vessel wall has become weakened, damaged, or both, may requiresubstantial support frame structure and/or outwardly-directed radialforce, such as that provided by a support frame capable of serving astenting function.

Both self-expandable support frames and support frames requiring aninput of force to effect expansion, such as balloon expandable supportframes, can be used in valve devices according to the invention. Thestructural characteristics of both of these types of support frames areknown in the art, and are not detailed herein. Each type of supportframe has advantages and for any given application, one type may be moredesirable than other types based on a variety of considerations. Forexample, in the peripheral vasculature, vessels are generally morecompliant and typically experience dramatic changes in theircross-sectional shape during routine activity. Medical devices forimplantation in the peripheral vasculature should retain a degree offlexibility to accommodate these changes of the vasculature.Accordingly, valve devices according to the invention intended forimplantation in the peripheral vasculature, such as valve devices,advantageously include a self-expandable support frame. These supportframes, as is known in the art, are generally more flexible thanballoon-expandable support frames following deployment.

Suitable support frames can be made from a variety of materials and needonly be biocompatible or able to be made biocompatible. Examples ofsuitable materials include, without limitation, stainless steel, nickeltitanium (NiTi) alloys, e.g., nitinol, other shape memory and/orsuperelastic materials, molybdenum alloys, tantalum alloys, titaniumalloys, precious metal alloys, nickel chromium alloys, cobalt chromiumalloys, nickel cobalt chromium alloys, nickel cobalt chromium molybdenumalloys, nickel titanium chromium alloys, linear elastic Nitinol wires,polymers, and composite materials. Also, resorbable and bioremodellablematerials can be used. As used herein, the term “resorbable” refers tothe ability of a material to be absorbed into a tissue and/or body fluidupon contact with the tissue and/or body fluid. A number of resorbablematerials are known in the art, and any suitable resorbable material canbe used. Examples of suitable types of resorbable materials includeresorbable homopolymers, copolymers, or blends of resorbable polymers.Specific examples of suitable resorbable materials include poly-alphahydroxy acids such as polylactic acid, polylactide, polyglycolic acid(PGA), or polyglycolide; trimethlyene carbonate; polycaprolactone;poly-beta hydroxy acids such as polyhydroxybutyrate orpolyhydroxyvalerate; or other polymers such as polyphosphazines,polyorganophosphazines, polyanhydrides, polyesteramides,polyorthoesters, polyethylene oxide, polyester-ethers (e.g.,polydioxanone) or polyamino acids (e.g., poly-L-glutamic acid orpoly-L-lysine). There are also a number of naturally derived resorbablepolymers that may be suitable, including modified polysaccharides, suchas cellulose, chitin, and dextran, and modified proteins, such as fibrinand casein.

Stainless steel and nitinol are currently considered desirable materialsfor use in the support frame due at least to their biocompatibility,shapeability, and well-characterized nature. Also, cold drawn cobaltchromium alloys, such as ASTM F562 and ASTM F1058 (commercial examplesof which include MP35N™ and Elgiloy™, both of which are available fromFort Wayne Metals, Fort Wayne, Ind.; MP35N is a registered trademark ofSPS Technologies, Inc. (Jenkintown, Pa., USA); Elgiloy is a registeredtrademark of Combined Metals of Chicago LLC (Elk Grove Village, Ill.,USA)), are currently considered advantageous materials for the supportframe at least because they are non-magnetic materials that providebeneficial magnetic resonance imaging (MRI) compatability, and avoid MRIartifacts typically associated with some other materials, such asstainless steel.

Suitable support frames can also have a variety of shapes andconfigurations, including braided strands, helically wound strands, ringmembers, consecutively attached ring members, zig-zag members, tubularmembers, and frames cut from solid tubes.

Examples of suitable support frames for use in medical devices accordingto the invention include those described in U.S. Pat. No. 6,464,720 toBoatman et al. for a RADIALLY EXPANDABLE STENT; U.S. Pat. No. 6,231,598to Berry et al. for a RADIALLY EXPANDABLE STENT; U.S. Pat. No. 6,299,635to Frantzen for a RADIALLY EXPANDABLE NON-AXIALLY CONTRACTING SURGICALSTENT; U.S. Pat. No. 4,580,568 to Gianturco for a PERCUTANEOUSENDOVASCULAR STENT AND METHOD FOR INSERTION THEREOF; and publishedapplications for United States Patent 20010039450 to Pavcnik et al. foran IMPLANTABLE VASCULAR DEVICE, 20040260389 to Case et al. forARTIFICIAL VALVE PROSTHESIS WITH IMPROVED FLOW DYNAMICS; 20070038291 TOCase et al. for INTRALUMINALLY-IMPLANTABLE FRAMES; 20070162103 to Caseet al. for IMPLANTABLE DEVICE WITH REMODELLABLE MATERIAL AND COVERINGMATERIAL; 20070100435 to Case et al. for ARTIFICIAL PROSTHESIS WITHPREFERRED GEOMETRIES; and 20070021826 to Case et al. for INTRALUMINALLYIMPLANTABLE FRAMES, each of which is hereby incorporated by reference inits entirety for the purpose of describing suitable support frames foruse in medical devices according to the invention.

The inclusion of a support frame in the valve devices according toembodiments of the invention is considered advantageous at least becauseit facilitates anchoring of the valve device at a point of treatment ina body vessel. Additionally, the support frame is believed to aid inplacing the bioprosthetic valve in a beneficial 3D configuration thatassists the valve device in achieving the benefits provided by thebioprosthetic valve.

The embodiments illustrated in FIGS. 3 through 8 include support frameshaving particularly advantageous structural features.

FIGS. 3 through 5 illustrate a valve device 300 according to a firstexemplary embodiment. The valve device 300 includes a support frame 310and a bioprosthetic valve 312 attached to the support frame 310.

Support frame 310 is described in detail in U.S. Pat. No. 6,508,833 toPavcnik et al. for a MULTIPLE-SIDED INTRALUMINAL MEDICAL DEVICE, whichis hereby incorporated by reference in its entirety for the purpose ofdescribing suitable support frames for use in valve devices according tothe invention. This support frame 310 is described briefly herein as anexample of a suitable support frame for use in valve devices accordingto the invention.

The support frame 310 is made of resilient material, preferably metalwire formed from stainless steel or a superelastic alloy, such asnitinol. While round wire is depicted in the figures, other types, suchas flat, square, triangular, D-shaped, and delta-shaped wire, may beused to form the frame 310. In the illustrated embodiment, the frame 310comprises a single strut 314 configured into a closed circumference 316.The closed circumference 316 includes four sides 318, 320, 322, 324 ofapproximately equal length. Alternative embodiments include frames withsides of different lengths, and frames of any polygonal shape, such aspentagon, hexagon, and octagon shapes.

The sides 318, 320, 322, 324 are interconnected by bends, each of whichcan comprise a coil 326 in the material of the support frame 310, or asimple bend 328. Alternative bend embodiments include outward-projectingfillets and inward-projecting fillets comprising a series of curves.Fillets are well known in the stent art as a means for reducing stressesin bends.

The cross-sectional diameter of the wire selected will depend on thesize of the medical device and the application. Wire that is too stiffcan damage the vessel, not conform well to the vessel wall, and increasethe profile of the device when loaded in a delivery system prior todeployment. Wire that is not sufficiently stiff may not allow the valveleaflet to function as desired. Furthermore, excessiveoutwardly-directed radial force may not be desirable in certainsituation and/or at points of treatment having certain characteristics,as described above. The specific wire selected for a particularembodiment will depend on these and other considerations.Advantageously, the wire selected will provide the desired attachment tothe bioprosthetic valve 312 and will allow a positive healing responseto occur in the surrounding tissue or at least not inhibit such aresponse.

The single piece of material comprising the frame 310 is formed into theclosed circumference 316 by securing the first and second ends 330, 332with an attachment mechanism 334, such as a metal cannula. The ends 330,332 are inserted into the cannula 334 and secured with a bondingelement, such as solder, an adhesive, or other suitable bonding element.Also, a mechanical bond can be formed between the ends 330, 332 andattachment mechanism 334 by crimping, deformation of adjacent elements,or any other suitable technique. Also, the ends 330, 332 can be joineddirectly to each other without addition of an attachment mechanism, suchas by soldering, welding, or other suitable methods to join material.Also alternatively, the frame 310 can be fabricated as a single piece ofmaterial by stamping or cutting a pattern from a sheet such as with alaser, fabricating from a mold, or some similar method of producing aunitary frame. Furthermore, the support frame 310 can be constructed toinclude structural elements that facilitate attachment and securement ofthe bioprosthetic valve 312 to the support frame 310, such as hooks,barbs, microbarbs, and other means for attaching tissue to a supportframe, as is currently known or hereinafter developed.

When deployed in a lumen of a vessel, the support frame 310 exerts aradially outward force on the interior wall of the vessel. The bendingstresses introduced to the frame 310 apply force radially outwardagainst the vessel wall to hold the frame 310 in place and preventvessel closure.

The bioprosthetic valve 312 includes a single leaflet 350 and acontiguous wall portion 352 of adjoining tissue. The leaflet 350 isattached to the contiguous wall portion 352 at attachment region 354. Afree edge 356 of the leaflet 350 moves in response to differingpressures in the body vessel in which the bioprosthetic valve isdisposed to effect opening and closing of the bioprosthetic valve 312.

In this embodiment, the bioprosthetic valve 312 is attached to thesupport frame by a suture 358 that extends along the entire length ofthe outer edge of the contiguous wall portion 352. While not illustratedin the Figures, additional connecting struts can be included in thesupport frame 310 to provide a full attachment path that extends alongthe entire outer edge of the contiguous wall portion 352 of thebioprosthetic valve 312.

The suture 358 advantageously comprises a single suture with no breaksor other interruptions along its length. The use of a single suture isconsidered advantageous at least because it avoids the presence ofunnecessary knots, breaks and other structures that may present animpediment to fluid flow in a body vessel in which the valve device 300is implanted. It is noted, though, that multiple sutures may be usedand, indeed, may be desirable in valve devices according to particularembodiments.

Also advantageously, the suture 358 extends through only a partialthickness of the contiguous wall portion 352 in at least one passthrough the contiguous wall portion 352. In particular embodiments, thesuture 358 is exposed on the external surface of the bioprosthetic valve310 but, because it passes only through a partial thickness of thecontiguous wall portion 352, is not exposed on the internal surface ofthe valve 310. This is considered advantageous at least because iteliminates potential structure that may present an impediment to fluidflow and because it reduces the potential for thrombus formation on theinternal surfaces of the valve 310, which is exposed to the blood whenthe valve device 300 is implanted in a body vessel. It is consideredparticularly advantageous to have the suture 358 extend through only apartial thickness of the contiguous wall portion 352 in substantiallyall of the passes through the contiguous wall portion 352. Currently, itis considered most advantageous to have the suture 358 extend throughonly a partial thickness of the contiguous wall portion 352 in all ofthe passes through the contiguous wall portion 352.

While FIGS. 3 through 5 illustrate a suture 358, it is noted that anysuitable attachment element or means for attaching tissue to a supportframe can be used to attach the bioprosthetic valve 312 to the supportframe 310, including clips, adhesives, tissue solder, and other suitablestructures, compositions, and techniques known in the art or hereinafterdeveloped.

FIG. 4 illustrates the valve device 300 in an open configuration. Inthis configuration, the free edge 356 of the leaflet 350 has movedtoward the contiguous wall portion 352, essentially collapsing againstit and creating an open space 360 within the valve device 300. The openspace 360 provides an open flow path in a body vessel when the valvedevice 300 is implanted therein.

FIG. 5 illustrates the valve device 300 in a closed configuration. Inthis configuration, the free edge 356 of the leaflet 350 has moved awayfrom the contiguous wall portion 352 in response to a pressure changeand/or flow reversal. In this embodiment, the leaflet 350 and an innerportion 370 of the contiguous wall portion 352 define a valve pocket380. When the valve device 300 is in this configuration, the valvepocket 380 collects fluid and substantially prevents flow through thevalve device 300, and through the body vessel, in the reverse, orantegrade, direction. It is noted that complete prevention of reversefluid flow is not necessary for the valve device 300 to functionproperly and, as described above, the desired degree of prevention canbe optimized by selection of an appropriate leaflet 350 with a size thatwill enable the desired degree of valve closure in operation.

FIGS. 6 and 7 illustrate a valve device 400 according to a secondexemplary embodiment. The valve device 400 includes a support frame 410and a bioprosthetic valve 412 attached to the support frame 410.

The support frame 410 is a self-expandable support frame comprisingproximal 414 and distal 416 portions connected by various connectorsegments 430, 440. The proximal portion 414 defines a first serpentinepath 418 that extends around the circumference of the support frame 410.The distal portion 416 defines a second serpentine path 420 that alsoextends around the circumference of the support frame 410. Eachserpentine path 418, 420 includes straight strut portions 422 that areinterconnected by bends 424. Each serpentine path also includessecondary bends 426 that substantially mirror bends 424 on the path. Thesupport frame 410 advantageously includes conventional structuralfeatures that facilitate anchoring, such as barbs 428, and structuralfeatures, such as radiopaque markers 429, that facilitate visualizationof the valve device 400 in conventional or other medical visualizationtechniques, such as radiography, fluoroscopy, and other techniques.

In the illustrated embodiment, each of the connector segments 430, 440include first and second struts that are substantially straight anddisposed substantially parallel to each other. This arrangement ofstruts in the connector segments 430, 440 is considered advantageous atleast because it provides a degree of structural redundancy and gives asecondary attachment point for the bioprosthetic valve 412 along thelength of the connector segments 430, 440. In embodiments in which themeans for attaching the bioprosthetic valve 412 to the support frame 410extends through only a partial thickness of the tissue of thebioprosthetic valve, this secondary attachment point can be used at anypoint along the length of the segments 430, 440 when a first attempt topass through a partial thickness of the tissue is unsuccessful. Theinventors have discovered that this is particularly advantageous invalve devices in which the bioprosthetic valve is attached to thesupport frame using one or more sutures 480.

In the illustrated embodiment, one connector segment 430 defines anoutwardly-projecting curve. When the valve device 400 is implanted in abody vessel, the curve forces a part of the vessel wall outward, whichdefines a sinus at the point of implantation. This structural feature isconsidered advantageous at least because the provision of a sinus isbelieved to aid in the opening and closing of the bioprosthetic valve412 by creating flow patterns that facilitate movement of the free edge476 of the leaflet 470, which may enhance the overall performance of thevalve device 400. It is believed to be advantageous to attach thecontiguous wall portion 472 of the bioprosthetic valve 412 to theconnector segment 430 defining the outwardly projecting curve. It isbelieved to be particularly advantageous to form a continuous attachmentbetween the contiguous wall portion 472 and the connector segment 430defining the outwardly projecting curve, such as by suturing along thelength of the curve and/or connector segment, at least because this isexpected to ensure a more complete definition of the sinus region in thevalve device 400 and to enhance securement of the bioprosthetic valve412 to the support frame 410.

The embodiment illustrated in FIGS. 6 and 7 include a support frame 410having three connector segments 430, 440, 450. Connector segment 430defines the curve, as described above, and is disposed substantiallyopposite to the inside surface of the leaflet 470 of the bioprostheticvalve 412. Connector segments 440, 450 are disposed substantiallyopposite to each other and near the attachment region 474 at which theleaflet 470 is attached to the contiguous wall portion 472. Also, asbest illustrated in FIG. 8 , connector segments 440, 450 lack a curveand are disposed substantially parallel to each other. This structuralarrangement ensures that the valve pocket formed when the bioprostheticvalve 412 is in the closed configuration is not shallowly formed andthat the leaflet 470 is able to sealingly interact with the vessel wall.

As best illustrated in FIG. 6 , the underside of the support frame 410,which represents the side disposed substantially opposite an exteriorsurface 478 of the leaflet 470, lacks a connector segment. Instead, thisside of the support frame 410 is largely open. This structuralarrangement is considered advantageous at least because it enables thefree edge 476 of the leaflet 470 to interact with the vessel wall duringclosure of the bioprosthetic valve 412, which is believed to result inbetter sealing and prevention of fluid flow in the reverse directionwhen the bioprosthetic valve 412 is in the closed configuration. Thisconfiguration is also expected to minimize wear of the leaflet edge 476because it avoids abrasion that might result if the edge 476 wereallowed to interact with a portion of the support frame 410.

It is noted that, while the illustrated support frame 410 includes threeconnector segments 430, 440, 450, any suitable number can be used andthe specific number chosen for a particular valve device according to anembodiment of the invention will depend on various considerations,including the nature and size of the bioprosthetic valve 412 and thenature and size of the body vessel into which the valve device isintended to be implanted. Also, while the illustrated connector segmentsare disposed substantially equidistant from each other, it is noted thatany suitable arrangement can be used and the specific arrangement chosenfor a particular valve device according to an embodiment of theinvention will depend on various considerations, including the natureand size of the bioprosthetic valve 412 and the nature and size of thecontiguous wall portion 472 of the valve 412.

In the embodiments illustrated in FIGS. 6 and 7 , the bioprostheticvalve 412 is attached to the support frame 410 in a manner such that thevalve is normally open, i.e., the free edge 476 of the leaflet 470 iscollapsed against the contiguous wall portion, thereby allowing fluidflow to pass through the lumen of the valve device 400 and the vessel inwhich it is implanted. As best illustrated in FIG. 6 , the valve 410closes only when a pressure head develops on an antegrade side of thevalve 410 that is sufficient to force the free edge 476 of the leaflet470 away from the contiguous wall portion 472 and adjacent wall of thebody vessel and toward, and potentially against, the opposing wall ofthe body vessel. In this configuration, a valve pocket 490 is formedthat fills with fluid until the valve 410 returns to its openconfiguration, which can occur in response to a change in the fluidpressure differential across the valve 410, a change in fluid flowdirection, or both.

It is noted that, although the embodiments illustrated in FIGS. 3through 7 include a single leaflet, it is expressly understood that abioprosthetic valve having two or more leaflets can be used in the valvedevices according to the invention. For example, for valve devicesintended to be used in body vessels having relatively large internaldiameters (e.g., vessels with diameters greater than 16 mm, such asadult human jugular and iliac veins), it may be advantageous to use abioprosthetic valve that includes two or more leaflets attached to acontiguous wall portion. In these embodiments, the contiguous wallportion need not include any commissure(s) between the leaflets.Multi-leaflet bioprosthetic valves are advantageously attached to thesupport frame such that the free edges of the leaflets are able to coaptwith each other such that the leaflets can close a valve opening formedinside the lumen of the valve device. A multi-leaflet bioprostheticvalve can be prepared from a single, xenogeneic valve having multipleleaflets by excising two or more leaflets from the valve while retaininga contiguous wall portion with the leaflets. The resulting bioprostheticvalve can then be attached to a support frame as described to provide avalve device. Also, a bioprosthetic valve can comprise multiple leafletsselected from multiple xenogeneic valves that are attached to thesupport frame to form a valve device. In these embodiments, two or moreleaflets, each having a contiguous wall portion, are selected from twoor more xenogeneic valves. The leaflets are attached to a single supportframe such that the free edges of the leaflets coapt in a manner thatcloses a valve opening formed between the leaflets. In theseembodiments, each leaflet is advantageously a noncoronary leaflet, forreasons described below. For valve devices that include a multi-leafletbioprosthetic valve and a support frame such as that illustrated inFIGS. 6 and 7 , it is expected to be advantageous to eliminate thestrutless window portion by including an additional connector segment,such as segments 430, 440, 450, in the frame and to position one or moreadditional sinus-defining structural features, such as connector segment430, opposite the additional leaflets.

Methods of making valve devices suitable for implantation in a patient,such as a human or other animal, are also provided.

A first step of an exemplary method comprises fabricating abioprosthetic valve. In one exemplary method, the fabrication is done inaccordance with the method described in incorporated U.S.Non-provisional patent application Ser. No. 12/252,253. In this method,a xenogeneic valve is harvested and fixed using suitable techniques,such as by fixing the valve with gluteraldehyde or any other suitablecross-linking agent. Examples of suitable fixation techniques aredescribed in U.S. Pat. No. 4,800,603 to Jaffe for TISSUE FIXATION WITHVAPOR; U.S. Pat. No. 5,595,571 to Jaffe and Hancock for BIOLOGICALMATERIAL PRE-FIXATION TREATMENT; U.S. Pat. No. 5,720,777 to Jaffe andHancock for BIOLOGICAL MATERIAL PRE-FIXATION TREATMENT; U.S. Pat. No.5,843,180 to Jaffe and Hancock for METHOD OF TREATING A MAMMAL HAVING ADEFECTIVE HEART VALVE; and U.S. Pat. No. 5,843,181 to Jaffe and Hancockfor BIOLOGICAL MATERIAL PRE-FIXATION TREATMENT, each of which is herebyincorporated by reference in its entirety for the purpose of describingsuitable techniques for fixing a xenogeneic valve for inclusion in avalve device according to the disclosure.

The use of a fixed valve is considered advantageous at least because thefixation process renders the tissue resistant to thrombosis whilemaintaining desirable compliance and mechanical properties of the valve.The use of a fixed valve aids in the handling of the valve during thefabrication method and may also enhance the performance of the resultingvalve device. A fabrication step in which a xenogeneic valve is firstfixed by exposure to gluteraldehyde followed by an irradiation step isconsidered particularly advantageous at least because the resultingbioprosthetic valve is sterile and has desirable compliance properties.

Tissue processed using the same procedures used by Hancock-JaffeLaboratories of Irvine, Calif., to fabricate prosthetic heart valves maybe used in the fabrication of bioprosthetic valves for use in themethods and apparatuses of the present invention.

In an exemplary fabrication method, a suitable xenogeneic valve isprovided and a suitable leaflet of the valve is selected based onvarious considerations, including the size and configuration of thevessel in which the valve device will be implanted. When a xenogeneicaortic valve, such as an aortic valve, is being used, selecting aleaflet that is associated with the noncoronary sinus, also known as theposterior aortic sinus, is considered advantageous at least because thewall portion contiguous with this leaflet does not include an opening toa vessel originating from the sinus. While it is preferred to select anoncoronary leaflet, it is noted that a coronary sinus leaflet can beselected and used and, in some circumstances, may even be desired. Forexample, the opening can be closed using appropriate techniques.Alternatively, the opening can be used to provide an attachment point atwhich the contiguous wall portion can be attached to the host vessel, ifdesired.

Once a suitable leaflet is selected, tissue is excised and/or trimmed toleave a contiguous wall portion that includes the attachment regionwhere the leaflet attaches to the vessel wall. As described above, thewall portion can comprise a minimal section of tissue, such as theportion illustrated in FIG. 2C, or a larger patch of contiguous tissuethat extends axially and circumferentially beyond the leaflet. Any othersuitable size and configuration can be used for the contiguous wallportion and a skilled artisan will be able to select an appropriate sizeand configuration based on various considerations, including the size ofthe valve device being made and the vessel in which the device is to beimplanted. At a minimum, the wall portion should include the attachmentregion where the leaflet attaches to the vessel wall. As describedabove, it is considered particularly advantageous to retain the naturalmargins of attachment between the leaflet and the vessel wall in thecontiguous wall portion.

In an optional step, the thickness of the contiguous wall portion can bereduced following harvesting and prior to attachment to a support frame.Any suitable technique for reducing tissue thickness can be used,including shaving, manual dissection, delamination, and othertechniques. Use of this step is believed to be advantageous at leastbecause it reduces the overall profile of the bioprosthetic valve, whichcan minimize bulk in the resulting valve device, and can provide aconsistent thickness to the wall portion. If this step is used, at leastthe margins of attachment between the leaflet and vessel wall should beretained to provide the desirable microstructure located in these areas,as described above. Also, it is noted that it may be advantageous toreduce the thickness of one or more of the axial edges of the contiguouswall portion, with respect to the lengthwise axis of the body vesselwithin which the bioprosthetic valve is intended to be used, such that atapered thickness is provided. The edges can be reduced to a minimalthickness that gradually tapers to a suitable thickness at theattachment region where the leaflet is attached to the contiguous wallportion which substantially retains the margins of attachment betweenthe leaflet and wall portion. Reducing the thickness of the one or moreaxial edges of the contiguous wall portion in this manner is believed tobe advantageous at least because it may remove one or more blunt edgesthat could provide a surface for clot formation or otherwise impedefluid flow once the bioprosthetic valve is positioned within a bodyvessel.

A second step of the exemplary method of making valve devices suitablefor implantation in a patient comprises attaching the bioprostheticvalve to a support frame. In exemplary methods, the step attaching thebioprosthetic valve to a support frame is accomplished by connecting thebioprosthetic valve to the support frame using a single suture. Inexemplary methods, a suture or other suitable means for attaching iscaused to extend through only a partial thickness of the contiguous wallportion in at least one of the passes through the contiguous wallportion. In exemplary methods, the suture or other suitable means forattaching is caused to extend through only a partial thickness of thecontiguous wall portion in substantially all of the passes through thecontiguous wall portion. In exemplary methods, the suture or othersuitable means for attaching is caused to extend through only a partialthickness of the contiguous wall portion in all of the passes throughthe contiguous wall portion.

Also, in exemplary methods, the contiguous wall portion advantageouslyis attached to the support frame along the entire outer edge of thecontiguous wall portion. In exemplary methods, a substantiallycontinuous attachment is formed along the entire outer edge of thecontiguous wall portion. Also in exemplary methods, the contiguous wallportion is attached to a sinus-defining feature of the support frame,such as an outwardly-projecting curve or other structural feature. It isbelieved to be advantageous to form a continuous attachment between thecontiguous wall portion and such a structural feature, such as bysuturing the wall portion along substantially the entire length of thestructural feature, or along the entire length of the structural featureat least because this is expected to ensure a more complete definitionof the sinus region in the valve device and to enhance securement of thebioprosthetic valve to the support frame.

Another exemplary method of making a valve device suitable forimplantation in a patient comprises the steps of excising a xenogeneicvalve from a host; fixing the valve using a suitable fixation technique,such as exposing the valve to gluteraldehyde or other suitable fixative;attaching the valve to a suitable support frame; trimming the valve toform a bioprosthetic valve as described herein; placing the valve devicein a suitable storage medium, such as physiological saline; andirradiating the valve device. It is noted that the step of trimming theexcised valve can be conducted before or after the valve is attached tothe support frame. Conducting this step before the valve has beenattached to the support frame is considered advantageous at leastbecause doing so eliminates potential interference by the frame duringthe trimming process.

The invention also provides methods of treating venous insufficiency. Anexemplary method comprises the steps of providing a valve deviceaccording to an embodiment of the invention and implanting the valvedevice in a body vessel of a patient containing at least oneinsufficient natural valve. In exemplary methods, the implanting step isaccomplished by percutaneously delivering the valve device to a point oftreatment in the body vessel and deploying the valve device at the pointof treatment. In these exemplary methods, the valve device is loadedinto a suitable percutaneous delivery system, which is then used todelivery the valve device to the point of treatment within the bodyvessel at which the valve device is to be deployed and implanted. Anysuitable percutaneous delivery system can be used, and the deliverysystem selected need only be able to accommodate the valve device in acompressed configuration and accomplish the desired delivery to thepoint of treatment within the body vessel. Conventional pusher-typedelivery systems that include a pusher and/or dilator with a surroundingsheath and that define a chamber into which the valve device can beloaded for delivery are considered suitable. When selecting a deliverysystem, care should be taken to ensure that the delivery system canaccommodate the bulk of the bioprosthetic valve when the valve device isloaded into the delivery system.

Other examples of suitable delivery systems include those described inUnited States Patent Application Publication No. 20080221656 to Hartleyet al. for ENDOVASCULAR DEPLOYMENT DEVICE; 20070088424 to Greenberg etal. for ENDOLUMINAL DELIVERY ASSEMBLY; 20060004433 TO Greenberg et al.for THORACIC DEPLOYMENT DEVICE AND STENT GRAFT; 20040230287 to Hartleyet al. for BRANCH STENT GRAFT DEPLOYMENT AND METHOD; 20040098079 toHartley et al. for THORACIC AORTIC STENT GRAFT DEPLOYMENT DEVICE; AND20030225446 to Hartley for MULTI-PIECE PROSTHESIS DEPLOYMENT APPARATUS,each of which is hereby incorporated by reference in its entirety forthe purpose of describing suitable delivery systems for use with thevalve devices described herein.

In other exemplary methods, the implanting step is accomplished bysurgically placing the valve device at a point of treatment in a bodyvessel.

EXAMPLE

Hemodynamic Evaluation of Valve Device

To evaluate the hydrodynamic performance and leaflet motioncharacteristics of a venous valve device according to the disclosure,several valve devices of various sizes were constructed and tested inthe aortic chamber of a pulsatile flow heart valve test apparatus.Hydrodynamic performance was observed under a range of conditionstypical of the upper leg of a human being. Leaflet function (i.e.,opening and closing) was confirmed for all valve devices under all testconditions studied.

a. Construction of Valve Devices

Three unconstrained diameters (10 mm, 12 mm, and 14 mm) believed to besuitable for valve devices intended to be implanted in a human vein wereselected for evaluation. For each unconstrained diameter, three valvedevices were constructed by attaching a gluteraldehyde crosslinkedbioprosthetic valve to a support frame by suturing. All specimens weresubmerged in saline following construction and subjected to irradiation.

b. Simulation of Compression for Loading into Percutaneous DeliverySystem

All specimens were loaded into a delivery catheter as shown in the TableI, and held in the compressed delivery configuration for at least 60(sixty) minutes prior to testing.

TABLE I Valve device unconstrained diameters and delivery sheath Frenchsize for simulation of loading compression Valve device unconstraineddiameter (mm) Delivery sheath French size (Fr) 10 14 12 16 14 18

c. Test System and Parameters

Each valve device evaluated in the aortic chamber of a pulsatile flowapparatus from ViVitro Systems, Inc. (Victoria, British Columbia,Canada). Each valve device was sutured into a section of silicone tubingsized so as not to constrain the valve device. Arterial pressure wasadjusted to achieve the desired static pressure. Table II providesdetailed conditions under which the pulsatile flow analysis wasconducted for each valve device.

TABLE II Pulsatile flow test conditions Parameter Condition Testsolution Physiological saline maintained at 37 ± 1° C. Cycle rate 30 bbmCardiac output 1.2 L/min Static pressure 15 mmHG ± 1, 35 mmHG ± 1, 50mmHg ± 1, 100 mmHG ± 1 Single stroke 70% with leaflet in open position,30% with wave form leaflet in closed position

d. Results

The valve devices were observed and visually recorded on video takenfrom the outflow aspect of the valve device. Confirmation of opening andclosing of the leaflet of each valve device was made through visualreview of video recordings of the pulsatile flow test. Table IIIpresents a summary of the visual confirmations.

TABLE III Leaflet function based upon review of video recording ofpulsatile flow test Leaflet opening and closing confirmed Valve.Diameter 15 35 50 100 device No (mm) mmHG mmHG mmHg mmHg 1 10 yes yesyes yes 2 10 yes yes yes yes 3 10 yes yes yes yes 4 12 yes yes yes yes 512 yes yes yes yes 6 12 yes yes yes yes 7 14 yes yes yes yes 8 14 yesyes yes yes 9 14 yes yes yes yes

e. Conclusion

Based on these results, it was concluded that the valve devices made inaccordance with the disclosure and tested as detailed above demonstratedacceptable leaflet function over the range of hemodynamic conditionsevaluated.

The foregoing detailed description provides exemplary embodiments of theinvention and includes the best mode for practicing the invention. Thedescription and illustration of embodiments is intended only to provideexamples of the invention and not to limit the scope of the invention,or its protection, in any manner.

What is claimed is:
 1. A support frame for implantation in a recipientvessel, said support frame having a longitudinal axis and comprising: afirst connector segment, a second connector segment, and a thirdconnector segment, the first connector segment disposed substantiallyopposite the second connector segment with respect to said longitudinalaxis, the first connector segment and the second connector segmentsubstantially parallel to each other, the third connector segmentdisposed circumferentially between the first connector segment and thesecond connector segment with respect to said longitudinal axis, thethird connector segment defining an outwardly-projecting curve extendingaway from the longitudinal axis; and a proximal portion and a distalportion, the proximal portion and the distal portion connected by thefirst connector segment, the second connector segment, and the thirdconnector segment; wherein the outwardly-projecting curve extends fromthe proximal portion toward the distal portion and away from thelongitudinal axis when implanted in said recipient vessel.
 2. Thesupport frame of claim 1, wherein the outwardly-projecting curve createsa sinus region when implanted in said recipient vessel.
 3. The supportframe of claim 1, further comprising a window portion free of aconnector segment, the window portion disposed between the firstconnector segment and the second connector segment; and wherein thewindow portion is disposed substantially opposite the third connectorsegment.
 4. The support frame of claim 1, wherein the third connectorsegment is disposed in a plane that contains the longitudinal axis. 5.The support frame of claim 1, wherein the proximal portion comprises aclosed circumference; and wherein the distal portion comprises a closedcircumference.
 6. The support frame of claim 1, wherein the proximalportion and the distal portion comprise consecutively attached ringmembers.
 7. The support frame of claim 1, wherein the first connectorsegment, the second connector segment, and the third connector segmentare formed of a cobalt chromium alloy.
 8. The support frame of claim 1,wherein the first connector segment, the second connector segment, andthe third connector segment are formed from a flat wire.
 9. The supportframe of claim 1, wherein the first connector segment, the secondconnector segment, and the third connector segment are formed from asingle piece of material.
 10. A support frame for implantation in arecipient vessel, said support frame having a longitudinal axis andcomprising: a first connector segment, a second connector segment, and athird connector segment, the first connector segment disposedsubstantially opposite the second connector segment with respect to saidlongitudinal axis, the first connector segment and the second connectorsegment substantially parallel to each other, the third connectorsegment disposed circumferentially between the first connector segmentand the second connector segment with respect to said longitudinal axis,the third connector segment defining an outwardly-projecting curveextending away from the longitudinal axis; and a proximal portion and adistal portion, the proximal portion and the distal portion connected bythe first connector segment, the second connector segment, and the thirdconnector segment; wherein outwardly-projecting curve extends from thedistal portion toward the proximal portion and away from thelongitudinal axis when implanted in said recipient vessel.
 11. Thesupport frame of claim 10, wherein the outwardly-projecting curvecreates a sinus region when implanted in said recipient vessel.
 12. Thesupport frame of claim 10, further comprising a window portion free of aconnector segment, the window portion disposed between the firstconnector segment and the second connector segment; and wherein thewindow portion is disposed substantially opposite the third connectorsegment.
 13. The support frame of claim 10, wherein the third connectorsegment is disposed in a plane that contains the longitudinal axis. 14.The support frame of claim 10, wherein the proximal portion comprises aclosed circumference; and wherein the distal portion comprises a closedcircumference.
 15. The support frame of claim 10, wherein the proximalportion and the distal portion comprise consecutively attached ringmembers.
 16. The support frame of claim 10, wherein the first connectorsegment, the second connector segment, and the third connector segmentare formed of a cobalt chromium alloy.
 17. The support frame of claim10, wherein the first connector segment, the second connector segment,and the third connector segment are formed from a flat wire.
 18. Thesupport frame of claim 10, wherein the first connector segment, thesecond connector segment, and the third connector segment are formedfrom a single piece of material.